Functional genomics relies heavily on high-throughput and the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery.
Recently, the first human protein histidine phosphatase (PHP1) has been identified (Apperson et al.: J. Neurosci. 16: p6839, 1996). The enzyme was isolated from rabbit liver extracts and characterized. In human cell lines PHP1 is displayed in the cytoplasma. Functional studies with the orthologue protein in C. elegans showed a neuronal localization (Kennedy et al.: Trends Biochem. Sci, 20: p350, 1995) (Kennedy et al.: Trends Neurosci, 20: p264, 1997) (Kennedy et al.: Brain Res. Brain Res. Rev, 26: p243, 1998) (Kennedy et al.: Science, 290: p750, 2000) (Kornau et al.: Curr. Opin. Neurobiol, 7: p368, 1997). The C. elegans homologue of PHP1 has been localized in motor- and pharyngeal sensorineurons MC, M3 and 12. The analogy from a nematode's pharynx to the human heart is described (PNAS 95,5072-5, 1998) thus, PHP1 and ligand could be relevant for various cardiovascular diseases. PHP1 is furthermore expressed in skeletal muscle, kidney, liver and brain. Additional references referring to PHP1 includes (Omkumar et al.: J. Biol. Chem, 271: p31670, 1996) (Ouyang et al.: J. Neurosci, 19: p7823, 1999) (Walikonis et al.: J. Neurosci, 20: p4069, 2000) (Walikonis et al.: J. Neurosci, 21: p423, 2001) (Zang et al.: J. Neurosci, 19: p96, 1999. (Legouis et al.: Nature Cell Biol, 2: p415, 2000)
In the current application protein interaction studies with PHP1 have been used in combination with DNA sequencing technologies and bioinformatics to identify gene sequences and gene functions that are ligands and interaction partners of PHP-1 on a molecular level.